Device for trapping rare cells from fluid samples

Abstract

A system for collecting biomarkers from a fluid stream includes a collection vessel having at least one fluid port that is adapted to be in fluid communication with the fluid stream. The collection vessel defines an inner volume. A 3D scaffold is disposed within the inner volume of the collection vessel. The 3D scaffold is chemically functionalized to bind the biomarkers in the fluid stream, wherein the biomarkers are eukaryotic cells of interest, extracellular vesicles associated with the eukaryotic cells of interest, or combinations thereof. A fluid driver circulates the fluid stream through the collection vessel via the at least one fluid port such that the fluid stream interacts with the 3D scaffold.

What is claimed is: 
     
         1 . A system for collecting biomarkers from a fluid stream, the system comprising:
 a collection vessel having at least one fluid port that is adapted to be in fluid communication with the fluid stream, the collection vessel defining an inner volume;   a 3D scaffold disposed within the inner volume of the collection vessel, the 3D scaffold being chemically functionalized to bind the biomarkers in the fluid stream, wherein the biomarkers are eukaryotic cells of interest, extracellular vesicles associated with the eukaryotic cells of interest, or combinations thereof; and   a fluid driver that is adapted to circulate the fluid stream through the collection vessel via the at least one fluid port such that the fluid stream interacts with the 3D scaffold.   
     
     
         2 . The system of  claim 1 , wherein the 3D scaffold is chemically functionalized to bind uniquely to the biomarkers. 
     
     
         3 . The system of  claim 1 , wherein each of the at least one fluid port is in fluid communication with a bore of a cannula or a lumen of a needle. 
     
     
         4 . The system of  claim 1 , wherein the 3D scaffold comprises beads, fibers, mesoporous structures, or combinations thereof. 
     
     
         5 . The system of  claim 1 , wherein a smallest dimension of the 3D scaffold is larger in size than biological cells in the fluid stream. 
     
     
         6 . The system of  claim 1 , wherein a material of the 3D scaffold comprises silica, glass, quartz, polymer plastics, dielectrics, silicon nitride, gallium nitride, polyethylene glycol, ceramics, or combinations thereof. 
     
     
         7 . The system of  claim 1 , wherein the 3D scaffold has a volume of at least 1 mL. 
     
     
         8 . The system of  claim 1 , wherein the 3D scaffold is functionalized by one or more linker chemistries comprising amine-functionalization, thiol-maleimide, or biotin-streptavidin. 
     
     
         9 . The system of  claim 1 , wherein the 3D scaffold carries targeting compounds that comprise folic acid, RGD peptide, antibodies, peptidomimetics, small molecules, or combinations thereof. 
     
     
         10 . The system of  claim 1 , wherein the 3D scaffold carries targeting compounds that are adapted to bind to EpCAM, EGFR, folate receptors, PSMA, or combinations thereof. 
     
     
         11 . The system of  claim 1 , wherein the fluid driver has a flow rate of at least 1 mL/minute. 
     
     
         12 . The system of  claim 1 , wherein the biomarkers are released from the 3D scaffold using an elution buffer. 
     
     
         13 . The system of  claim 1 , wherein the collection vessel comprises an inlet and an outlet, and wherein the fluid driver draws fluid in via the inlet and exhausts the fluid via the outlet. 
     
     
         14 . The system of  claim 1 , wherein the fluid driver draws fluid in and exhausts fluid via a common fluid port. 
     
     
         15 . The system of  claim 1 , wherein the fluid driver comprises a fluid pump, a reciprocating plunger, or a variable pressure chamber. 
     
     
         16 . A method of collecting biomarkers, the method comprising:
 connecting at least one fluid port of a collection vessel to a source of fluid, the collection vessel carrying a 3D scaffold within an inner volume defined by the collection vessel, the 3D scaffold being chemically functionalized to bind the biomarkers in a fluid stream, wherein the biomarkers are eukaryotic cells of interest, extracellular vesicles associated with the eukaryotic cells of interest, or combinations thereof;   circulating a fluid stream from the source of fluid through the collection vessel such that the fluid stream interacts with the 3D scaffold and such that the 3D scaffold binds to the biomarkers carried in the fluid stream, wherein at least 10 mL of fluid circulates through the collection vessel;   returning the fluid stream to the source of the fluid; and   releasing the biomarkers from the 3D scaffold into a sample vial.   
     
     
         17 . The method of  claim 16 , wherein connecting the at least one fluid port to a source of fluid comprises using a cannula or a needle. 
     
     
         18 . The method of  claim 16 , wherein at least 100 mL is circulated through the collection vessel. 
     
     
         19 . The method of  claim 16 , wherein the 3D scaffold is functionalized by one or more linker chemistries comprises amine-functionalization, thiol-maleimide, or biotin-streptavidin. 
     
     
         20 . The method of  claim 16 , wherein the 3D scaffold carries targeting compounds that comprise folic acid, RGD peptide, antibodies, peptidomimetics, small molecules, or combinations thereof. 
     
     
         21 . The method of  claim 16 , wherein the 3D scaffold carries targeting compounds that are adapted to bind to EpCAM, EGFR, folate receptors, PSMA, or combinations thereof. 
     
     
         22 . The method of  claim 16 , wherein fluid is circulated through the collection vessel at a rate of at least 1 mL/minute. 
     
     
         23 . The method of  claim 16 , further comprising the step of releasing the cells of interest using an elution buffer. 
     
     
         24 . The method of  claim 16 , wherein the 3D scaffold is chemically functionalized to bind uniquely to the biomarkers such that the sample collected comprises a higher concentration of the biomarkers while maintaining or reducing relative concentrations of background components in the fluid stream.